PROTAC ERRα ligand 1

PROTAC ERRα ligand 1 is a PROTAC target protein ligand. PROTAC ERRα ligand 1 is an orally active ERRα inverse agonist with IC₅₀ values of 0.6 μM for ERRα. PROTAC ERRα ligand 1 shows no significant activity against a panel of other nuclear receptors, including ERα^c, ERRγ, ERβ, PPARα, PPARγ, PPARδ, and RXRα. PROTAC ERRα ligand 1 can provide enhanced insulin sensitivity in vivo. PROTAC ERRα ligand 1 can be used for metabolic diseases research, such as type 2 diabetes and obesity^[1]. IC50 & Target:Ligand for E3 Ligase^[1] In Vitro: PROTAC ERRα ligand 1 (compound 29) (24 h) inhibits ERRα with an IC₅₀ of 0.6 μM in a two-hybrid reporter assay in HEK293 cells^[1].
PROTAC ERRα ligand 1 (10 μM) exhibits a clean off-target profile, showing no significant inhibition of CYP3A4, CYP2D6, or a broad panel of 51 receptors and ion channels^[1].
PROTAC ERRα ligand 1 (15 μM, 24 h) shows no functional activity against PPARα, PPARγ, PPARδ and RXRα in HEK293 cells^[1].
PROTAC ERRα ligand 1 (4-18 h) proves much less potent (>50-fold selectivity) at inhibiting coactivator peptide binding with ERRγ and does not compete with PPARγ ligand binding at test concentrations up to 10 μM^[1].
PROTAC ERRα ligand 1 (15 μM, 0-6 days) shows no functional estrogenic or anti-estrogenic activity in reporter gene and MCF-7 cell proliferation assays^[1]. In Vivo: PROTAC ERRα ligand 1 (3, 10 and 30 mg/kg, p.o., b.i.d. for 5 days or q.d. for 15 days) leads to the normalization of serum triglyceride and insulin levels as well as an improvement in glucose tolerance in diet-induced obesity (DIO) mouse models^[1].
PROTAC ERRα ligand 1 (0.08-10 mg/kg, p.o., q.d. for 12 or 25 days) markedly enhances insulin sensitivity, normalizing glucose levels in Zucker diabetic fatty (ZDF) rat models^[1].